Major Advance: Novel DNA Cancer-Associated Variants Identified

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A global scientific consortium released a study yesterday that has identified up to 80 new regions of the genome associated with an increased susceptibility to developing breast, prostate, and ovarian cancers. The conclusions are drawn from the collaborative work of more than 50 groups around the world, who carried out genotyping activities in four different centers and whose work was coordinated by Javier Benítez, Ph.D., director of the Human Cancer Genetics Program at the Spanish National Cancer Research Centre (CNIO). The teams used high-throughput genotyping methods to carry out their work.

Researchers from the European Collaborative Oncological Gen-Environmental Study (COGS) project published a total of 12 articles in several prestigious journals including Nature Genetics, Nature Communications, The American Journal of Human Genetics, and PLOS Genetics. To identify those genetic variants that might increase the risk of suffering from cancer among the general population, the project's investigators more than 200,000 single nucleotide polymorphisms (SNPs) selected from the genome of 100,000 breast, prostate, and ovarian cancer patients, as well as from 100,000 control cases without cancer.

The authors of the different studies identified 41 new genes or regions of the genome that may be susceptible to contributing to the development of breast cancer, 23 new ones for prostate cancer, and four for ovarian cancer.

“Specifically, the 41 new genes identified for breast cancer increase to almost 70 the number of genes that indicate a high probability of developing this illness when mutated,” explains Dr. Benítez, adding that “these data indicate that up to 5% of the general population may have a high risk of suffering from this illness at some point in their lives.”

“We’re now on the verge of being able to use our knowledge to develop tests that could complement breast cancer screening and take us a step closer to having an effective prostate cancer screening program,” says Doug Easton, Ph.D., of the University of Cambridge, U.K., who has led several of the presented studies.

Among all of the genes identified, there are some that could help cancerous cells to spread throughout the body, others would favor the uncontrolled growth of cells, and still others would help by removing the brakes that stop cells from growing, continued Dr. Benítez.

The authors of the study have also identified TERT as the gene susceptible to breast and ovarian cancer. This finding complements a recent study by researchers in Spain that was published in Nature Genetics, which relates the role of telomeres and their protective function of DNA with the development of chronic lymphocytic leukemia.

According to scientists, a big surprise to come out of the study is the identification of thousands of additional genes to those described to date that, to a lesser extent, make someone more susceptible to cancer. “In the case of breast cancer, we have discovered up to 1,000 genes that increase the risk of suffering the illness only very slightly, but when accumulated, they could explain its appearance in some patients,” notes Dr. Benítez.

These results show the enormous complexity of cancer. One example would be hereditary breast cancer, which correlates in most cases with mutations in the BRCA1 and BRCA2 genes. These tumors, however, could be explained by the accumulation of multiple mutations in genes that when appearing alone slightly increase the risk of developing cancer. “These genes would explain why many families have these types of hereditary cancers without the presence of mutations in the BRCA genes,” continues Benítez. “Every tumor is born with its own distinct genetic history, so if we identify those individuals whose genetic characteristics confer them a greater probability of developing cancer, we will be able to provide them with more adequate follow-up and thus reduce the appearance of the disease or diagnose it in its initial phases.”

The collaborative effort of thousands of national and international scientists has opened new perspectives for cancer research, offering new clues to the understanding of the molecular pathways in cancer cells, according to Dr. Benítez, who adds that these studies could also expand the possibilities in the search for new therapeutic treatments against cancer.

Officials at Illumina reported that the company’s iCOGS custom array was used to identify genetic variants related to breast, ovary, and prostate cancer as part of the study. Specifically, the iCOGS array identifies SNPs across selected regions of DNA associated with cancer. Its 200,000 SNPs were drawn from previous genome-wide association studies of the different cancer types and subtypes, associations with disease survival or other traits that are associated with risk of cancer, and functional candidates. The technology was used to test more than 200,000 individuals participating in the COGS.

The main aims of the European COGS project are directed towards the study of the genetic and environmental factors that predispose people to the appearance of breast, prostate, and ovarian cancers, the most common forms of cancer in developing countries, and towards how society might benefit from such results. The European COGS project is the result of the collaboration between four international consortiums: BCAC, whose aim is to study breast cancer; PRACTICAL, which researches genetic alterations associated with prostate cancer; OCAC, whose aim is to study ovarian cancer; and CIMBA, which studies BRCA1 and BRCA2 modifications.